Comprehensive whole-genome sequence analyses provide insights into the genomic architecture of cerebral palsy.

We performed whole-genome sequencing (WGS) in 327 children with cerebral palsy (CP) and their biological parents. We classified 37 of 327 (11.3%) children as having pathogenic/likely pathogenic (P/LP) variants and 58 of 327 (17.

Moral distress among acute mental health nurses: A systematic review.

Moral distress has been identified as an occupational hazard for clinicians caring for vulnerable populations. The aim of this systematic review was (i) to summarize the literature reporting on prevalence of, and factors related to, moral distress among nurses within acute mental health settings, and (ii) to examine the efficacy of interventions designed to address moral distress among nurses within this clinical setting. A comprehensive literature search was conducted in October 2022 utilizing Nursing & Allied Health, Embase, CINAHL, PsychInfo, and PubMed databases to identify eligible studies published in English from January 2000 to October 2022.

Pediatric popper intoxication: Case report of intoxication in a 3-month-old infant.

We present the case of a 3-month-old boy who accidentally ingested poppers. The patient presented with refractory hypoxemia and compensated circulatory failure associated with severe methemoglobinemia. He made a full recovery after treatment with the specific antidote methylene blue.

Divergent Temporal Trends of Mercury in Arctic Char from Paired Lakes Influenced by Climate-Related Drivers.

Climate-driven changes including rising air temperatures, enhanced permafrost degradation, and altered precipitation patterns can have profound effects on contaminants, such as mercury (Hg), in High Arctic lakes. Two physically similar lakes, East Lake and West Lake at the Cape Bounty Arctic Watershed Observatory on Melville Island, Nunavut, Canada are being affected by climate change differently. Both lakes have experienced permafrost degradation in their catchments; however, West Lake has also undergone multiple underwater Mass Movement Events (MMEs; beginning in fall 2008), leading to a sustained 50-fold increase in turbidity.

Disruption of DDX53 coding sequence has limited impact on iPSC-derived human NGN2 neurons.

Background: The X-linked PTCHD1 locus is strongly associated with autism spectrum disorder (ASD). Males who carry chromosome microdeletions of PTCHD1 antisense long non-coding RNA (PTCHD1-AS)/DEAD-box helicase 53 (DDX53) have ASD, or a sub-clinical form called Broader Autism Phenotype. If the deletion extends beyond PTCHD1-AS/DDX53 to the next gene, PTCHD1, which is protein-coding, the individuals typically have ASD and intellectual disability (ID).

Mutational Landscape of Autism Spectrum Disorder Brain Tissue.

Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes.

Hemiplegic Migraine Associated With Variations: A Clinical and Genetic Study.

Background And Objective: variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands.

Methods: was analyzed in 860 probands with hemiplegic migraine, and variations were identified in 30 probands.

Genome sequencing for detection of pathogenic deep intronic variation: A clinical case report illustrating opportunities and challenges.

Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7-year-old male with a similar presentation found by research-based quad genome sequencing to have two novel splicing variants in trans in JAM3, including one deep intronic variant (NM_032801.4: c.

Emerging dominance of summer rainfall driving High Arctic terrestrial-aquatic connectivity.

Hydrological transformations induced by climate warming are causing Arctic annual fluvial energy to shift from skewed (snowmelt-dominated) to multimodal (snowmelt- and rainfall-dominated) distributions. We integrated decade-long hydrometeorological and biogeochemical data from the High Arctic to show that shifts in the timing and magnitude of annual discharge patterns and stream power budgets are causing Arctic material transfer regimes to undergo fundamental changes. Increased late summer rainfall enhanced terrestrial-aquatic connectivity for dissolved and particulate material fluxes.

Canadian permafrost stores large pools of ammonium and optically distinct dissolved organic matter.

Permafrost degradation may lead to mobilization of carbon and nutrients and enhance microbial processing rates of previously frozen organic matter. Although the pool size and chemical composition of dissolved organic matter (DOM) are fundamental determinants of the carbon cycle in Arctic watersheds, its source within the seasonally thawing active layer and the underlying permafrost remains largely uncharacterized. Here, we used 25 soil cores that extended down into the permafrost from nine sites across Arctic Canada to quantify dissolved organic carbon (DOC) and nitrogen stocks, and to characterize DOM optical properties.

Differential impact of thermal and physical permafrost disturbances on High Arctic dissolved and particulate fluvial fluxes.

Climate warming and changing precipitation patterns have thermally (active layer deepening) and physically (permafrost-thaw related mass movements) disturbed permafrost-underlain watersheds across much of the Arctic, increasing the transfer of dissolved and particulate material from terrestrial to aquatic ecosystems. We examined the multiyear (2006-2017) impact of thermal and physical permafrost disturbances on all of the major components of fluvial flux. Thermal disturbances increased the flux of dissolved organic carbon (DOC), but localized physical disturbances decreased multiyear DOC flux.

A novel intronic variant in UBE3A identified by genome sequencing in a patient with an atypical presentation of Angelman syndrome.

Angelman syndrome (AS) is a genetic neurodevelopmental disorder caused by loss or deficient expression of UBE3A on the maternally inherited allele. In 10-15% of individuals with a clinical diagnosis of AS, a molecular diagnosis cannot be established with conventional testing. We describe a 13-year-old male with an atypical presentation of AS, who was found to have a novel, maternally inherited, intronic variant in UBE3A (c.

Snow Deposition and Melting as Drivers of Polychlorinated Biphenyls and Organochlorine Pesticides in Arctic Rivers, Lakes, and Ocean.

Concurrent sampling of freshwater (lakes and rivers), seawater, snow, air, and zooplankton for a range of legacy polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) was undertaken in the Canadian High Arctic during ice-covered, melting, and ice-free conditions. Overall, there was a general trend of higher fluvial PCB/OCP concentrations associated with the spring snow melt (early-mid June), while much lower concentrations were detected during the snow-free season (end of July). In contrast, PCB concentrations in two Arctic lakes (West and East Lakes, Melville Island) and in ocean waters, sharply increased in the ice-free period, likely because of inputs from the ice/snow layer melting and river runoff.

A large data resource of genomic copy number variation across neurodevelopmental disorders.

Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted to identify shared etiology among NDDs, but this is the first genome-wide CNV analysis across autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and obsessive-compulsive disorder (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ, 1,838 ASD, 427 ADHD and 222 OCD) and 1,769 family members, mainly parents.

Legacy and Emerging Persistent Organic Pollutants (POPs) in Terrestrial Compartments in the High Arctic: Sorption and Secondary Sources.

Legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and emerging perfluoroalkyl substances (PFASs) were measured in vegetation and soil samples collected at remote lakes in the Canadian High Arctic. Field studies were carried out in 2015 and 2016 to assess concentrations of POPs, study the relevant sorbing phases, and determine whether Arctic soils were sinks or sources of legacy POPs to the atmosphere and to neighboring lakes. The patterns of legacy POPs in vegetation and soils were dominated by low molecular weight PCB congeners along with OCPs, confirming the importance of long-range atmospheric transport.

The world's largest High Arctic lake responds rapidly to climate warming.

Using a whole-watershed approach and a combination of historical, contemporary, modeled and paleolimnological datasets, we show that the High Arctic's largest lake by volume (Lake Hazen) has succumbed to climate warming with only a ~1 °C relative increase in summer air temperatures. This warming deepened the soil active layer and triggered large mass losses from the watershed's glaciers, resulting in a ~10 times increase in delivery of glacial meltwaters, sediment, organic carbon and legacy contaminants to Lake Hazen, a >70% decrease in lake water residence time, and near certainty of summer ice-free conditions. Concomitantly, the community assemblage of diatom primary producers in the lake shifted dramatically with declining ice cover, from shoreline benthic to open-water planktonic species, and the physiological condition of the only fish species in the lake, Arctic Char, declined significantly.

Copy number variation in fetal alcohol spectrum disorder.

Fetal alcohol spectrum disorder (FASD) is characterized by a combination of neurological, developmental, and congenital defects that may occur as a consequence of prenatal alcohol exposure. Earlier reports showed that large chromosomal anomalies may link to FASD. Here, we examined the prevalence and types of copy number variations (CNVs) in FASD cases previously diagnosed by a multidisciplinary FASD team in sites across Canada.

OTUD7A Regulates Neurodevelopmental Phenotypes in the 15q13.3 Microdeletion Syndrome.

Copy-number variations (CNVs) are strong risk factors for neurodevelopmental and psychiatric disorders. The 15q13.3 microdeletion syndrome region contains up to ten genes and is associated with numerous conditions, including autism spectrum disorder (ASD), epilepsy, schizophrenia, and intellectual disability; however, the mechanisms underlying the pathogenesis of 15q13.

Differences in Riverine and Pond Water Dissolved Organic Matter Composition and Sources in Canadian High Arctic Watersheds Affected by Active Layer Detachments.

Regional warming has caused permafrost thermokarst and disturbances, such as active layer detachments (ALDs), which may alter carbon feedback in Arctic ecosystems. However, it is currently unclear how these disturbances alter DOM biogeochemistry in rivers and ponds in Arctic ecosystems. Water samples from the main river channel, ALD-disturbed/undisturbed tributaries, and disturbed/undisturbed ponds within a catchment in the Canadian High Arctic were collected and analyzed using carbon isotopes and spectroscopic methods.

Germline and somatic mutations in with diverse neurodevelopmental phenotypes.

Objective: To expand the clinical phenotype associated with gene mutations and to understand the effect of mutations in the pathogenesis of focal cortical dysplasia (FCD).

Methods: Patients with mutations were identified in various ways: as part of a retrospective cohort study of epileptic encephalopathy; through clinical referrals of individuals (10,619) with developmental delay (DD) for chromosomal microarray; and from a collection of 5,205 individuals with autism spectrum disorder (ASD) examined by whole-genome sequencing.

Results: Seven patients with heterozygous de novo mutations affecting the coding region of were newly identified.

Climate and permafrost effects on the chemistry and ecosystems of High Arctic Lakes.

Permafrost exerts an important control over hydrological processes in Arctic landscapes and lakes. Recent warming and summer precipitation has the potential to alter water availability and quality in this environment through thermal perturbation of near surface permafrost and increased mobility of previously frozen solutes to Arctic freshwaters. We present a unique thirteen-year record (2003-16) of the physiochemical properties of two High Arctic lakes and show that the concentration of major ions, especially SO, has rapidly increased up to 500% since 2008.

Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature.

Background: Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a multisystem inborn error of metabolism.

Objectives: To better characterise the natural history of PMM2-CDG.

Methods: Medical charts of 96 patients with PMM2-CDG (86 families, 41 males, 55 females) were retrospectively reviewed.